Abstract
BackgroundMucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs).MethodsA diagnosis of MPS II or Hunter syndrome was performed based on the following approach after a clinical and paraclinical suspicion. Two biochemical and molecular tests were carried out separately and according to the availability of the biological material.ResultsAll patients in this cohort presented the most common MPS II clinical features. Electrophoresis of GAGs on a cellulose acetate plate in the presence of a high concentration of heparane sulfate showed an abnormal dermatan sulfate band in the patients compared with that in a control case. Furthermore, leukocyte IDS activity ranged from 0.00 to 0.75 nmol/h/mg of leukocyte protein in patients.Five previously reported mutations were identified in this study patients: one splice site mutation, c.240 + 1G > A; two missense mutations, p.R88P and p.G94D; a large deletion of exon 1 to exon 7; and one nonsense mutation, p.Q396*. In addition, two novel alterations were identified in the MPS II patients: one frame shift mutation, p.D450Nfs*95 and one nonsense mutation, p.Q204*.Additionally, five known IDS polymorphisms were identified in the patients: c.419–16 delT, c.641C > T (p.T214M), c.438 C > T (p.T146T), c.709-87G > A, and c.1006 + 38 T > C.ConclusionsThe high level of urine GAGs and the deficiency of iduronate 2-sulfatase activity was associated with the phenotype expression of Hunter syndrome. Molecular testing was useful for the patients’ phenotypic classification and the detection of carriers.
Highlights
Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs)
Biochemical analysis confirmed the diagnosis of all MPS II patients included in the study
The twelve Tunisian MPS II patients in the present study presented low or undetectable levels ofIDS activity (0.00 to 0.75 nmol/ h/mg of leukocyte proteins) (Table 2)
Summary
Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs). Hunter syndrome (MPS II; OMIM 309900) is an Xlinked recessive inborn error that causes deficient activity of iduronate 2-sulfatase (IDS, EC3.1.6.13). This lysosomal enzyme hydrolyses the 2 sulfate groups of the Liduronate 2-sulfate units, dermatan sulfate and heparan sulfate [1]. The severe phenotype of MPS II, the neuropathic form, is characterized by a progressive clinical deterioration with neurological involvement, multiple dysostosis including joint stiffness, coarse facies including broad noses, macroglossia, and cardiovascular involvement that often leads to death before 15 years of age. In the most attenuated form of MPS II, diagnosis may not be made until 10 years of age, and death may occur in early adulthood; some patients have survived until their fifth or sixth decades of life [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
